Abstract
OCT4 (octamer-binding transcription factor) is a transcription factor responsible for maintaining the pluripotent properties of embryonic stem cells. In this paper, we present the results of studies to investigate the role of the OCT4 splicing variant in urothelial bladder cancer and the relationship between the OCT4 phenotype and the morphological parameters of tumor malignancy. Ninety patients who received a cystectomy for bladder cancer were enrolled. The expression of OCT4 protein was analyzed by immunohistochemistry. The ratio of OCT4-positive cells was the lowest in pT1 (pathological assessment (p)—tumor extent confined to mucosa (T1)) tumors and the highest in pTis (non-papillary tumor extent confined to urothelium) and pT2 (tumor extent including muscularis propria) tumors. Information about the percentage of OCT4A-positive tumor cells could facilitate choosing the treatment mode in borderline pTis–pT1 (crossing the border of the basement membrane; the first stage of progression) and pT1–pT2 (crossing the border of the muscularis propria; the second stage of progression) cases: a higher percentage of OCT4A-positive cells should support more radical therapy. A significantly higher percentage of cases with moderate OCT4 intensity was found in metastasizing (the third stage of progression) cases with >2 positive lymph nodes. The percentage of OCT4-positive cells was significantly higher for cancers with a high grade, higher non-classic differentiation number and greater aggressiveness of invasion. The differentiation, maturation and aggressiveness of tumor invasion appear to depend on the expression of the OCT4 phenotype in cancer cells, similar to the successive stages of malignancy progression in urothelial cancer.
Highlights
Urothelial cancers are cancers of relatively unusual biology
We observed a significant variation in the percentage of OCT4A-positive cells in individual cases
Our study shows that the phenotype of OCT4A stem cells is strongly related to the histoclinical aspects of urothelial cancer malignancy
Summary
Urothelial cancers are cancers of relatively unusual biology. One group of urothelial cancers includes non-invasive cancers, such as papillary and in situ cancer, and another group includes invasive cancers that infiltrate the mucosa or muscularis propria (“non-muscle invasive” and “muscle invasive”, respectively) [1]. The diverse types of biological malignancy of urothelial bladder cancers forms the basis of the different clinical management standards, which include: (1) conservative management for papillary (pTa) and surface-infiltrating (pT1) cancers; (2) radical treatment for cancers infiltrating the deep layers (pT2–4); and (3) conservative and radical treatment for in situ cancers (pTis). Application of these treatment standards is clear for cases with well-defined progression. Researchers have focused on stem cells [8] and certain aspects of their biology in the process of carcinogenesis; e.g., origination of cancer stem cells [9]
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